Evidence map›Paper›PMID 33515487›Full record

ArticleImmunity2021

Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection.

Wenxi Xu, Laura M Snell, Mengdi Guo, Giselle Boukhaled, Bethany L Macleod, Ming Li, Michael V Tullius, Cynthia J Guidos, Ming-Sound Tsao, Maziar Divangahi and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.1field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Molecular signaling in coinfection: howFrontiers in immunology · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. CD4bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Article
  17. iScience · 2023
    Article
  18. Co-infection of mice with SARS-CoV-2 andFrontiers in immunology · 2023
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Wenxi XuPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
Laura M SnellPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
Mengdi GuoPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Giselle BoukhaledPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
Bethany L MacleodPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
Ming LiPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Michael V TulliusDepartment of Medicine and Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cynthia J GuidosProgram in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.
Ming-Sound TsaoPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
Maziar DivangahiMeakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Marcus A HorwitzDepartment of Medicine and Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jun LiuDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
David G BrooksPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: dbrooks@uhnresearch.ca.
University Health Network · CAUniversity of California, Los Angeles · USHospital for Sick Children · CAMcGill University Health Centre · CAUniversity of Toronto · CA

Funding

Mechanisms of Viral PersistenceR01AI085043 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BROOKS, DAVID G · 2010 to 2023
$4.5M
CIHR FDN148386NIAID NIH HHS R01 AI085043
6 · The paper itself

Abstract

Chronic viral infections increase severity of Mycobacterium tuberculosis (Mtb) coinfection. Here, we examined how chronic viral infections alter the pulmonary microenvironment to foster coinfection and worsen disease severity. We developed a coordinated system of chronic virus and Mtb infection that induced central clinical manifestations of coinfection, including increased Mtb burden, extra-pulmonary dissemination, and heightened mortality. These disease states were not due to chronic virus-induced immunosuppression or exhaustion; rather, increased amounts of the cytokine TNFα initially arrested pulmonary Mtb growth, impeding dendritic cell mediated antigen transportation to the lymph node and subverting immune-surveillance, allowing bacterial sanctuary. The cryptic Mtb replication delayed CD4 T cell priming, redirecting T helper (Th) 1 toward Th17 differentiation and increasing pulmonary neutrophilia, which diminished long-term survival. Temporally restoring CD4 T cell induction overcame these diverse disease sequelae to enhance Mtb control. Thus, Mtb co-opts TNFα from the chronic inflammatory environment to subvert immune-surveillance, avert early immune function, and foster long-term coinfection.

Indexed as

Adaptive ImmunityAnimalsChronic DiseaseCoinfectionImmunity, InnateLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, Inbred C57BLMice, TransgenicMycobacterium tuberculosisNeutrophilsPhagocytosisSeverity of Illness IndexTh17 CellsTh1 CellsCD4 T cellschronic viral infectioncoinfectionCyTOFLCMVMycobacterium tuberculosisneutrophilT cell differentiationTh17 cellsTh1 cells

Identifiers

PMID33515487
PMCPMC7946746
OpenAlexW3126777224

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.